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Published in: Acta Neuropathologica 3/2007

01-03-2007 | Original Paper

PIK3CA alterations in primary (de novo) and secondary glioblastomas

Authors: Daisuke Kita, Yasuhiro Yonekawa, Michael Weller, Hiroko Ohgaki

Published in: Acta Neuropathologica | Issue 3/2007

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Abstract

We assessed alterations in the EGFR/PTEN/PI3K pathway in 107 primary (de novo) glioblastomas and 32 secondary glioblastomas that progressed from low-grade or anaplastic astrocytomas. SSCP followed by DNA sequencing in exons 9 and 20 of the PIK3CA gene revealed missense mutations in 5/107 (5%) primary and 1/32 (3%) secondary glioblastomas. Quantitative real-time PCR showed PIK3CA amplification (>3 copy numbers) in 14/107 (13%) primary and 3/32 (9%) secondary glioblastomas. Only one glioblastoma showed both PIK3CA mutation and amplification. Taken together with previously published data on EGFR amplification and PTEN mutations, at least one alteration in the EGFR, PTEN, or PIK3CA genes was detected in 63% of primary glioblastomas, which was significantly more frequent than in secondary glioblastomas (31%; < 0.001). Furthermore, this signaling pathway was altered by either PTEN mutations or PIK3CA amplification in 10 of 12 (83%) malignant glioma cell lines analyzed. These results suggest that the EGFR/PTEN/PI3K pathway is frequently altered in glioblastomas and is a promising target for therapy, in particular for primary glioblastomas.
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Metadata
Title
PIK3CA alterations in primary (de novo) and secondary glioblastomas
Authors
Daisuke Kita
Yasuhiro Yonekawa
Michael Weller
Hiroko Ohgaki
Publication date
01-03-2007
Publisher
Springer-Verlag
Published in
Acta Neuropathologica / Issue 3/2007
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-006-0186-1

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